Genetic factors such as the immunoglobulin (Ig) V region genes and the major histocompatibility complex (MHC) have been shown to play important pathogenetic roles in systemic lupus erythematosus (SLE). Certain SLE associated autoantibodies are important in some clinical manifestations. One of them is specific for the Ro/SSA antigen, a RNA-protein complex of 100 KD molecular weight. The occurrence of anti-Ro/SSA antibodies has clinical implications. Because of the availability of two monoclonal anti-Ro/SSA IgG proteins, hybridoma antibodies has been generated to probe the V regions of these two Ig's. Preliminary data indicate that we have hybridoma antibodies against the private and crossreactive idiotypes of these proteins. More monoclonal antibodies which identify various V region markers of these two monoclonal anti-Ro/SSA Igs and the affinity purified polyclonal anti-Ro/SSA antibodies from SLE patients will be generated. These V region markers will be used to determine if a particular V region is associated with SLE renal disease. Correlative studies will reveal if these markers will define subsets of SLE. Emphasis will be placed on the anti-Ro/SSA antibodies in the serums of homozygous C2 deficient patient with an SLE-like syndrome. A cellular study will be initiated to determine the numbers of circulating lymphocyte bearing these markers and the proportions of circulating Ig secreting cells to be positive for these markers. An T cell dependent pokeweed mitogen induced Ig synthesis system and other cellular systems will be used to probe certain aspects of the regulation of this system. In a collaborative study, HLA studies will be performed on our SLE patients and their family members to clarify the role of MHC and the importance of the interaction between MHC and Ig genes in the pathogenesis of SLE. Results of this proposal will lead to new insights to SLE and related autoimmune disorders.